Application of unsaturated quaternary ammonium bisphosphonate in preparation of modified barium sulfate powder

Abstract

The invention provides an application of unsaturated quaternary ammonium bisphosphonate in preparation of modified barium sulfate powder. The molecular structure of the unsaturated bisphosphonate contains acryloyloxy or methacryloyloxy, quaternary ammonium cations, bisphosphonate or phosphonic acid betaine, and the unsaturated bisphosphonate is used as a surfactant, a modifier, an initiator and a solvent for preparing a barium sulfate powder material by a precipitation method. The precipitated barium sulfate powder can be endowed with antibacterial and bacteriostatic performance, medical efficacy of diphosphonate, water absorption performance in a medium and biocompatibility performance.

Description

Technical Field

[0001] The present invention relates to a preparation method of barium sulfate powder, and particularly relates to the application of a bisphosphonate containing an unsaturated quaternary ammonium cation in the molecular structure in the preparation of modified barium sulfate powder, belonging to the field of inorganic functional materials. Technical Background

[0002] Barium sulfate is an inexpensive, non-toxic, and biocompatible inorganic material. Its fine powder is an important component of polymethyl methacrylate (PMMA)-based bone cement as a developer. However, the interaction between barium sulfate powder and the condensed interface of PMMA polymer is weak, and the inorganic material and the polymer show phase separation. When the dosage of barium sulfate fine powder in PMMA-based bone cement exceeds 10% of the total mass, it will have an adverse impact on PMMA-based bone cement, such as an extended room-temperature curing time of PMMA-based bone cement; a decrease in the tensile strength, flexural strength, and fracture toughness of PMMA-based bone cement products; and an increase in the residual amount of methyl methacrylate (MMA) monomer in PMMA-based bone cement products. However, increasing the dosage of barium sulfate in PMMA-based bone cement: ① can significantly reduce the raw material cost of PMMA-based bone cement. ② can significantly reduce the elastic modulus of PMMA-based bone cement products. Professionals are familiar that the elastic modulus of PMMA is 3000 - 4000 mPa, much higher than the elastic modulus of trabecular bone, which is 100 - 700 MPa. This significant difference will produce a stress shielding effect and a change in stress load transfer, leading to an increased risk of adjacent vertebral fractures. ③ can significantly reduce the room-temperature curing volume shrinkage of PMMA-based bone cement. The MMA monomer with a density of 0.94 g / cm 3 is polymerized into PMMA polymer with a density equal to 1.19 g / cm 3 , resulting in volume shrinkage after implant filling, which is an important issue that must be concerned clinically. ④ can significantly improve the heat dissipation of PMMA-based bone cement curing exotherm. The heat released by the addition polymerization reaction of 1 gram of MMA monomer at room temperature in the liquid component of PMMA-based bone cement is as high as 560 joules. If the heat dissipation is poor, it will cause a significant increase in the temperature of the bone cement, which can be as high as 80 - 120 °C, leading to necrosis of bone cells and bone tissue near the bone cement. ⑤ can significantly improve the X-ray imaging effect and clarity of PMMA-based bone cement.

[0003] In order to solve the problem of phase separation between the inorganic material and the polymer, and improve the mechanical properties and service performance of the finished PMMA-based bone cement, scientific workers in many countries have carried out research and development. Most of them use γ-methacryloxypropylsilane coupling agent to modify the surface of barium sulfate powder, endowing the modified barium sulfate powder with surface chemical bonding groups, or improving its compatibility with the polymer, and improving the interfacial bonding force between the barium sulfate powder and the PMMA polymer. There are also coprecipitation modification methods using 3-(N,N-dimethyl-(2-(2-methacryloyloxy)ethyl)ammonium) propane-1-sulfonate inner salt, mono(2-methacryloyloxyethyl) phosphate, etc. with barium sulfate, so that the methacryloyloxy groups with polymerization reactivity are evenly embedded in the crystal gaps of barium sulfate or adsorbed on its surface. Then, by participating in the MMA room-temperature polymerization and curing process of the PMMA-based bone cement, the uniform dispersion of barium sulfate in PMMA is realized, the binding force between barium sulfate and PMMA is improved, the interfacial phenomenon between the inorganic powder material and the polymer is eliminated, and the antibacterial property of the PMMA-based bone cement can also be imparted at the same time, improving its bioactivity, and the effect is remarkable. There are also cases where nano-barium sulfate is used instead of barium sulfate fine powder for PMMA-based bone cement, achieving a significant improvement in the mechanical properties of the finished PMMA-based bone cement. Because nano-materials have many unique advantages such as small size effect, surface effect, and macroscopic quantum tunneling effect, they have high surface energy, larger specific surface area, more uniform particle size, and better dispersibility; however, the easy agglomeration of nano-particles is its obvious defect. In addition, the two main components in PMMA-based bone cement, PMMA and barium sulfate, both belong to implantable bio-inert materials, which can neither be biodegradable in the body nor have the function of stimulating or inducing the growth of bone cells and bone tissues. Moreover, compounding antibiotics in PMMA-based bone cement is of great significance for preventing and treating acute and chronic osteoarticular infections after surgeries such as implantable osteomyelitis, bone replacement, and fractures. Finally, compounding some bisphosphonates such as alendronate sodium or zoledronic acid sodium in PMMA-based bone cement has a positive effect on promoting the differentiation of osteoblasts and inhibiting the generation of osteoclasts. To sum up, the existing modifications of barium sulfate powder materials by blending methods or coprecipitation, etc. mostly aim at improving or enhancing its single property or function, and it is rare to consider multiple modification effects.

[0004] Based on the performance, functions, and usage requirements of barium sulfate powder materials in PMMA-based bone cement, aiming at the defects and deficiencies of existing modification methods and technologies for related barium sulfate powder materials, and to ensure the safe and stable applicability of PMMA-based bone cement, according to the chemical principle of molecular design, the present invention uses a bisphosphonate containing acryloyloxy quaternary ammonium cation in the molecular structure to modify the preparation process of precipitated barium sulfate powder materials. Thus, it is expected to endow PMMA-based bone cement with antibacterial and bacteriostatic properties, the medical efficacy of bisphosphonates, water absorption properties in the medium, and biocompatible properties, while improving the binding force between barium sulfate powder materials and PMMA polymers, and improving the tensile strength, flexural strength, and compressive strength of PMMA-based bone cement; increasing the addition amount of barium sulfate powder materials in PMMA-based bone cement, and reducing the curing heat effect and curing body shrinkage of PMMA-based bone cement. Summary of the Invention

[0005] The application of an unsaturated quaternary ammonium bisphosphonate described in the present invention in the preparation of modified barium sulfate powder is achieved through the following steps: successively weigh deionized water, unsaturated quaternary ammonium bisphosphonate, sulfate, and inhibitor and feed them into a reaction kettle; after filling the reaction kettle with nitrogen to remove oxygen, control the temperature at 20-100 °C, stir until the materials in the reaction kettle present a clear solution state, then slowly add an aqueous barium salt solution to the reaction kettle. After the feeding of the aqueous barium salt solution is completed, lower the temperature of the reaction system in the reaction kettle to -10-25 °C, age for 2-12 hours, and then separate, wash, and dry to obtain unsaturated quaternary ammonium bisphosphonate modified barium sulfate powder;

[0006] Wherein the unsaturated quaternary ammonium bisphosphonate has the structure shown in general formula (I):

[0007]

[0008] Wherein R in general formula (I) is selected from H or CH3, R1 is selected from C1-C 18 hydrocarbon group, M n+ is selected from Na + 、K + 、Ag + 、Ca 2+ 、Co 2+ 、Cu 2+ 、Fe 2+ 、Mg 2+ 、Mn 2+ 、Zn 2+ 、Sr 2+ 、Al 3+ 、Bi 3+ 、Cr 3+ 、Fe 3+ 、Sn 4+ 、Ti 4+ 、Zr 4+, one of N-benzyl-N,N,N-trimethylammonium cation, N-benzyl-N,N,N-triethylammonium cation, N-benzyl-N,N,N-tributylammonium cation, N,N,N,N-tetrabutylammonium cation, N-dodecyl-N,N-dimethyl-N-benzylammonium cation, N-dodecyl-N,N-diethyl-N-benzylammonium cation, N-tetradecyl-N,N-dimethyl-N-benzylammonium cation or N-tetradecyl-N,N-diethyl-N-benzylammonium cation, where n is selected from one of 1, 2, 3 or 4, X - is selected from Cl - , Br - or NO3 - and is one of them.

[0009] The sulfate salt refers to a water-soluble sulfate salt, specifically one or more of sodium sulfate, potassium sulfate, ammonium sulfate, magnesium sulfate, aluminum sulfate, and zinc sulfate.

[0010] The barium salt refers to a water-soluble barium salt, specifically one of barium chloride, barium bromide, and barium nitrate.

[0011] The inhibitor refers to vitamin C or 4-oxo-2,2,6,6-tetramethylpiperidine.

[0012] The dosage ratio of the unsaturated quaternary ammonium bisphosphonate / sulfate salt / barium salt / inhibitor / deionized water is 5 - 50:10 - 150:10 - 150:0.15 - 1.5:50 - 5000.

[0013] The aqueous barium salt solution refers to dissolving the barium salt in deionized water, filtering out insoluble impurities, and then preparing an aqueous barium salt solution with a mass percentage concentration of 0.2 - 250‰.

[0014] Professionals are well aware that the unsaturated quaternary ammonium bisphosphonate described in the present invention is a double salt, and its molecular structure contains various functional structural units, namely acryloyloxy or methacryloyloxy, quaternary ammonium cations, bisphosphonates, or phosphobetaines. Among them, acryloyloxy or methacryloyloxy has the characteristic of participating in the MMA polymerization reaction; if a long-chain quaternary ammonium cation or phosphobetaine is selected, it has the characteristics of hydrophilic water absorption, heat conduction, conductivity, antibacterial and bacteriostatic, surfactant, and low melting temperature; if the unsaturated quaternary ammonium bisphosphonate is selected as sodium unsaturated quaternary ammonium bisphosphonate, potassium unsaturated quaternary ammonium bisphosphonate, or magnesium unsaturated quaternary ammonium bisphosphonate, its water solubility at room temperature is very high, and it is expected to have the medical efficacy of medical bisphosphonates (such as alendronate sodium, risedronate sodium, neridronate sodium, olpadronate sodium, zoledronic acid, ibandronate sodium); if the sodium unsaturated quaternary ammonium bisphosphonate, potassium unsaturated quaternary ammonium bisphosphonate, or magnesium unsaturated quaternary ammonium bisphosphonate encounters various metal ions such as calcium ions, barium ions, strontium ions, silver ions, copper ions, and zinc ions, the precipitation effect and chelation coordination efficacy are strong, and the room temperature water solubility of the resulting unsaturated quaternary ammonium bisphosphonate is relatively small, and its solubility increases with the increase of water temperature. Among them, silver unsaturated quaternary ammonium bisphosphonate, copper unsaturated quaternary ammonium bisphosphonate, or zinc unsaturated quaternary ammonium bisphosphonate has the characteristic of slowly releasing silver ions, copper ions, or zinc ions in the room temperature water system environment, and together with the long-chain quaternary ammonium cation, it exhibits a synergistic, persistent, stable, and highly efficient antibacterial and bacteriostatic efficacy, and also shows high biological activity. In summary, professionals can expect that using the unsaturated quaternary ammonium bisphosphonate described in the present invention to modify precipitated barium sulfate powder can endow the latter with diverse physical, chemical, and biological characteristics. Detailed implementation mode

[0015] In order to further understand the present invention, it is specifically described by way of examples, and the purpose is to better understand the content of the present invention. Therefore, the unsaturated quaternary ammonium bisphosphonate-modified barium sulfate powder not listed in the examples should not be regarded as a limitation to the protection scope of the present invention.

[0016] Example 1 Preparation of formula-(1) unsaturated quaternary ammonium bisphosphonate

[0017] According to the method disclosed in CN202510168956.0 and the preparation steps shown in the following reaction formula, prepare formula-(1) unsaturated quaternary ammonium bisphosphonate:

[0018]

[0019] 36 g of ethanolamine and 80 g of 1,4-dioxane were charged into a reaction kettle, and the temperature of the materials in the reaction kettle was controlled at 20 - 25 °C. 102 g of diethyl vinylphosphonate was slowly added. After the addition of diethyl vinylphosphonate was completed, the temperature of the materials in the reaction kettle rose to 50 °C and stirred for 12 hours. Then 93 g of benzyl chloride was added, the temperature of the materials in the reaction kettle was raised to 80 - 90 °C, and stirring reaction continued for 12 hours. The temperature of the materials in the reaction kettle was lowered to room temperature, and 338.4 g of crude product was obtained by filtration. Through sampling and analysis, 87.3% of the components in the crude product were N-(2-hydroxyethyl)-N-benzyl-N,N-bis(2-(diethoxyphosphoryl)ethyl)ammonium chloride. From this, the yield of N-(2-hydroxyethyl)-N-benzyl-N,N-bis(2-(diethyloxyphosphoryl)ethyl)ammonium chloride calculated based on ethanolamine was 94.8%; 338.4 g of the said crude product was dissolved in 305 g of hydrochloric acid with a molar concentration of 5.5 M, and the temperature was controlled at 90 - 100 °C and stirred for hydrolysis reaction for 12 hours. The temperature of the hydrolysis reaction product was lowered to room temperature, and 300.7 g of crude N-(2-hydroxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid)ammonium chloride was obtained by filtration; 300.7 g of the crude N-(2-hydroxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid)ammonium chloride was dissolved in 250 g of deionized water, and the pH value was adjusted to 4.5 using an aqueous sodium hydroxide solution with a mass percentage concentration of 30%. When solid substances began to precipitate during rotary evaporation and concentration, the temperature was lowered and allowed to stand to precipitate solid products. After filtration, recrystallization with absolute ethanol, and vacuum drying at 40 - 50 °C to constant weight, 191.5 g of white crystal-like intermediate product was obtained. The elemental analysis (%) of this white crystal-like intermediate product: C 42.32, H 6.23, N 3.78, P 16.48, which was basically consistent with the calculated values of C 13 H 23 NO7P2: C 42.51, H 6.31, N 3.81, P 16.87; Its IR (KBr tablet, cm -1 ): 3453, 3346, 3021, 2923, 2873, 1638, 1546, 1445, 1362, 1256, 1108, 1037, 974, 926 were respectively attributed to the characteristic vibration absorption peaks of P - O - H, C - O - H, C═C - H, H - C - H, C═C, C - N, P═O, C - O, P - O. 1 H-NMR (TMS as internal standard, CD3OD, δ): 1.82 (t, 2H), 2.03 (s, 3H), 3.37 (t, 4H), 3.45 (t, 2H), 3.98 (t, 4H), 4.49 (t, 2H), 5.02 (s, 1H), 7.04 - 7.58 (m, 5H). From the elemental analysis, IR and 1The spectral analysis results of H-NMR confirmed that the white crystalline intermediate has the structural characteristics of N-(2-hydroxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid) ammonium shown by the following formula:

[0020]

[0021] Thereafter, at room temperature, 45 g of N-(2-hydroxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid) ammonium and 0.32 g of 2,6-di-tert-butylhydroquinone were dissolved in 105 g of 1,4-dioxane in a reaction kettle. After purging with nitrogen to remove oxygen, 20.2 g of methacryloyl chloride was added. The mixture was stirred for 2 hours for the esterification reaction. Then, the temperature of the esterification reaction was raised to 50-60 °C, and stirring was continued for 6 hours. The temperature was lowered, and the pH of the reaction product system in the reaction kettle was adjusted to 7.5 using an aqueous solution of caustic soda with a mass percentage concentration of 30%. The mixture was allowed to stand and the water-insoluble substances in the aqueous phase were removed. 158 g of an aqueous solution of silver nitrate with a mass percentage concentration of 25% was slowly added to the obtained organic phase. The mixture was stirred rapidly for 2 hours in the dark, filtered, washed with ethanol, and dried in vacuo to obtain a rice-colored solid product. The elemental analysis results (%) of the rice-colored solid product were: C 30.98, H 4.03, N 2.13, P 9.27, which were basically consistent with the calculated values of C 17 H 26 Ag2N2O 11 P2: C 31.41, H 4.03, N 2.15, P 9.53; its IR (KBr tablet, cm -1 ): 3542, 3346, 3019, 3017, 2924, 2867, 1724, 1636, 1543, 1437, 1259, 1163, 1036, 974 were respectively attributed to the characteristic vibration absorption peaks of P-O-H, C═C-H, C-H, C═O, C═C, C-N, P═O, C-O, P-O. 1 H-NMR (TMS as the internal standard, D2O, δ): 1.78 (m, 2H), 1.87 (s, 3H), 3.21 (m, 4H), 3.52 (t, 2H), 3.98 (t, 4H), 4.51 (s, 2H), 5.39-5.63 (m, 2H), 7.06-7.61 (m, 5H). Based on the comprehensive reasoning and judgment of its elemental analysis, IR, and 1 H-NMR analysis results, it was confirmed that the rice-white solid product has the structural characteristics of silver N-(2-methacryloyloxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid) ammonium dihydrate of formula-(1):

[0022]

[0023] Preparation of the unsaturated quaternary ammonium bisphosphonate of formula-(2) in Example 2

[0024] According to the method and operation steps of Example 1, replace benzyl chloride in Example 1 with 1-bromododecane and silver nitrate with zinc chloride, and finally obtain a white powdery product. Using the analysis and characterization method of Example 1, it is confirmed that the white powdery product has the structural characteristics of zinc N-(2-methacryloyloxyethyl)-N-dodecyl-N,N-bis(ethyl-2-phosphonic acid) ammonium chloride tetrahydrate of formula-(2):

[0025]

[0026] Preparation of unsaturated quaternary ammonium bisphosphonate of formula-(3) in Example 3

[0027] According to the method and operation steps of Example 1, replace benzyl chloride in Example 1 with 1-bromododecane and silver nitrate with calcium chloride, and finally obtain a white powdery product. Using the analysis and characterization method of Example 1, it is confirmed that the white powdery product has the structural characteristics of calcium N-(2-methacryloyloxyethyl)-N-dodecyl-N,N-bis(ethyl-2-phosphonic acid) ammonium chloride dihydrate of formula-(3):

[0028]

[0029] Preparation of unsaturated quaternary ammonium bisphosphonate of formula-(4) in Example 4

[0030] According to the method and operation steps of Example 1, replace silver nitrate in Example 1 with tetrabutylammonium bromide, and finally obtain a white crystalline product. Using the analysis and characterization method of Example 1, it is confirmed that the white crystalline product has the structural characteristics of N’,N’,N’,N’-tetrabutylammonium bromide-N-(2-methacryloyloxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid) ammonium of formula-(4):

[0031]

[0032] Modified barium sulfate powder (Ⅰ-1) in Example 5

[0033] Weigh 2.83 g of silver N-(2-methacryloyloxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonate) ammonium nitrate dihydrate of Example 1, 6.8 g of sodium sulfate decahydrate, and 0.018 g of 4-oxo-2,2,6,6-tetramethylpiperidine, and successively mix them into 265 g of deionized water in a reaction kettle. After purging with nitrogen to remove oxygen, raise the temperature of the materials in the reaction kettle to 50 - 60 °C. After stirring for 0.5 h, a clear solution state is presented; then slowly dropwise add 235 g of an aqueous solution containing 4.3 g of barium chloride into the reaction kettle. After 2 h, the feeding of the barium chloride aqueous solution is completed. Lower the temperature of the reaction system in the reaction kettle to -5 - -10 °C, age for 8 h, then centrifuge and wash with deionized water 2 - 3 times. Send the obtained powder product into a vacuum drying oven at 50 - 60 °C and dry for 12 h to obtain 6.72 g of white powder modified barium sulfate (Ⅰ-1).

[0034] In the IR (KBr tablet, cm -1 ) spectrum of the white powder modified barium sulfate (Ⅰ-1) compared with pure barium sulfate, characteristic absorption peaks are present at 3022 (w), 2974 (w), 2886 (w), 1726 (m), 1636 (m), 1543 (m), 1258 (m), 1108 (s), indicating that the white powder modified barium sulfate (Ⅰ-1) contains structural units such as CH3, CH2, benzene ring, C=C, C=O, P=O, C-O, etc. It is confirmed that the white powder product is a coprecipitation powder material of silver N-(2-methacryloyloxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonate) ammonium nitrate of formula-(1) and barium sulfate. The SEM of the white powder modified barium sulfate (Ⅰ-1) shows that it is irregular particles with a particle size of 93 - 300 nm. In addition, add a small amount of white powder modified barium sulfate (Ⅰ-1) to dilute bromine water. After ultrasonic oscillation at room temperature and sealing for 1 h, the deep red color of the bromine water gradually fades, and the white insoluble particles gradually turn into a light yellow color that cannot be eluted by water. It shows that the unsaturated C=C double bond in the white powder modified barium sulfate (Ⅰ-1) undergoes an addition reaction with bromine, making the color of the bromine water fade; at the same time, it may be that part of Br - reacts with the silver ions in the white powder modified barium sulfate (Ⅰ-1), resulting in the formation of light yellow silver bromide.

[0035] Modified barium sulfate powder (Ⅰ-1’) of Comparative Example 1

[0036] Weigh 2.83 g of silver N-(2-methacryloyloxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid) ammonium nitrate dihydrate of Example 1, 4.3 g of barium chloride, and 0.018 g of 4-oxo-2,2,6,6-tetramethylpiperidine. Mix them into 350 g of deionized water in a reaction kettle in sequence. After purging with nitrogen to remove oxygen, raise the temperature of the materials in the reaction kettle to 50 - 60 °C and stir for 0.5 h. The solution in the reaction kettle cannot present a clear solution state; then slowly add 250 g of an aqueous solution containing 4.8 g of sodium sulfate dropwise to the reaction kettle. After 2 h, the feeding of the sodium sulfate aqueous solution is completed. Lower the temperature of the reaction system in the reaction kettle to -5 - -10 °C, age for 8 h, then centrifuge and wash with deionized water 2 - 3 times. Send the obtained powder product to a vacuum drying oven at 50 - 60 °C and dry for 12 h to obtain 6.81 g of a white powder-like modified barium sulfate (Ⅰ-1’) product. SEM characterization shows that the white powder-like modified barium sulfate (Ⅰ-1’) product is small plate-like particles with a particle size of 65 - 1450 μm. The IR (KBr tablet, cm -1 ) spectrum of the white powder-like modified barium sulfate (Ⅰ-1’) product is basically the same as that of the white modified barium sulfate powder material (Ⅰ-1) in Example 5, indicating that the white powder-like modified barium sulfate (Ⅰ-1’) product contains structural units such as CH3, CH2, C=C, C=O, P=O, C-O, etc., and confirming that the white powder-like modified barium sulfate (Ⅰ-1’) product is a coprecipitation powder of silver N-(2-methacryloyloxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid) ammonium nitrate of formula-(1) and barium sulfate.

[0037] Example 6 Modified barium sulfate powder (Ⅰ-2)

[0038] According to the method and operation steps of Example 1, change silver N-(2-methacryloyloxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid) ammonium nitrate dihydrate of formula-(1) in Example 1 to zinc N-(2-methacryloyloxyethyl)-N-dodecyl-N,N-bis(ethyl-2-phosphonic acid) ammonium chloride tetrahydrate of formula-(2) to obtain 6.77 g of a white powder-like modified barium sulfate (Ⅰ-2) product. SEM characterization shows that the white powder-like modified barium sulfate (Ⅰ-2) product is irregular particles with a particle size of 0.15 - 0.65 μm. The IR (KBr tablet, cm -1)In the spectrum, characteristic absorption peaks are present at 2937(s), 2876(s), 1726(m), 1261(w), and 1108(m), indicating that the white powdery modified barium sulfate (Ⅰ-2) contains structural units such as CH3, CH2, C=O, P=O, and C-O. It is confirmed that the white powdery modified barium sulfate (Ⅰ-2) is a coprecipitated powder of calcium N-(2-methacryloyloxyethyl)-N-dodecyl-N,N-bis(ethyl-2-phosphonic acid) ammonium dichloride of formula-(3) and barium sulfate.

[0039] Example 7 Modified Barium Sulfate Powder (Ⅰ-3)

[0040] According to the method and operation steps of Example 1, replace silver N-(2-methacryloyloxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid) ammonium dinitrate of formula-(1) in Example 1 with calcium N-(2-methacryloyloxyethyl)-N-dodecyl-N,N-bis(ethyl-2-phosphonic acid) ammonium dichloride of formula-(3) to obtain 6.75 g of white powdery modified barium sulfate (Ⅰ-3) product. SEM characterization shows that the white powdery modified barium sulfate (Ⅰ-3) product is irregular particles with a particle size of 65 - 550 nm. The IR (KBr tablet, cm -1 )In the spectrum, characteristic absorption peaks are present at 2937(s), 2876(s), 1726(m), 1261(w), and 1108(m), indicating that the white powdery modified barium sulfate (Ⅰ-3) contains structural units such as CH3, CH2, C=O, P=O, and C-O. It is confirmed that the white powdery modified barium sulfate (Ⅰ-3) is a coprecipitated powder of calcium N-(2-methacryloyloxyethyl)-N-dodecyl-N,N-bis(ethyl-2-phosphonic acid) ammonium dichloride of formula-(3) and barium sulfate.

[0041] Example 8 Modified Barium Sulfate Powder (Ⅰ-4)

[0042] According to the method and operation steps of Example 1, replace silver N-(2-methacryloyloxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid) ammonium dinitrate of formula-(1) in Example 1 with N’,N’,N’,N’-tetrabutylammonium-N-(2-methacryloyloxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid) ammonium bromide of formula-(4) to obtain 5.98 g of white powdery modified barium sulfate (Ⅰ-4) product. SEM characterization shows that the white powdery modified barium sulfate (Ⅰ-4) product is irregular particles with a particle size of 60 - 180 nm. The IR (KBr tablet, cm -1)In the spectrum, characteristic absorption peaks are present at 2939(s), 2878(s), 1726(m), 1644(w), 1448(w), 1258(w), and 1108(s), indicating that the white powdery modified barium sulfate (Ⅰ-4) contains structural units such as CH3, CH2, benzene ring, C=O, P=O, and C-O. It is confirmed that the white powdery modified barium sulfate (Ⅰ-4) is a coprecipitated powder of N’,N’,N’,N’-tetrabutylammonium bromide-N-(2-methacryloyloxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid) ammonium of formula-(4) and barium sulfate.

[0043] Example 9 Modified barium sulfate powder (Ⅰ-5)

[0044] Weigh 2.83 grams of silver N-(2-methacryloyloxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid) ammonium dihydrate of formula-(1) from Example 1, 6.8 grams of sodium sulfate, and 0.018 grams of 4-oxo-2,2,6,6-tetramethylpiperidine, and mix them into 450 grams of deionized water in a reaction kettle in sequence. After purging with nitrogen to remove oxygen, raise the temperature of the materials in the reaction kettle to 50 - 60 °C. After stirring for 0.5 hours, it becomes a clear solution; then slowly add 550 grams of an aqueous solution containing 4.3 grams of barium chloride dropwise to the reaction kettle. After 2 hours, the addition of the barium chloride aqueous solution is completed. Lower the temperature of the reaction system in the reaction kettle to -5 - -10 °C, age for 8 hours, then centrifuge and wash with deionized water 2 - 3 times. Send the obtained powder product to a vacuum drying oven at 50 - 60 °C and dry for 12 hours to obtain 6.49 grams of white powdery modified barium sulfate powder (Ⅰ-5) product. The SEM of this modified barium sulfate powder (Ⅰ-5) shows that it is irregular particles with a particle size of 45 - 120 nm. The modified barium sulfate powder (Ⅰ-5) and the white modified barium sulfate powder (Ⅰ-1) in Example 5 have the same IR (KBr tablet, cm -1 ) spectrum, indicating that the modified barium sulfate powder (Ⅰ-5) contains structural units such as C=C, C=O, P=O, and C-O. It is confirmed that the white powder product is a coprecipitated powder of silver N-(2-methacryloyloxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonic acid) ammonium dihydrate of formula-(1) and barium sulfate.

[0045] Example 10 Modified barium sulfate powder (Ⅰ-6)

[0046] Weigh 2.85 g of zinc ammonium N-(2-methacryloyloxyethyl)-N-dodecyl-N,N-bis(ethyl-2-phosphonic acid) chloride dihydrate of Example 3, 8.8 g of sodium sulfate, and 0.018 g of 4-oxo-2,2,6,6-tetramethylpiperidine, and successively mix them into 450 g of deionized water in a reaction kettle. After purging with nitrogen to remove oxygen, raise the temperature of the materials in the reaction kettle to 50 - 60 °C. After stirring for 0.5 hour, a clear solution state is presented; then slowly add 550 g of an aqueous solution containing 4.3 g of barium chloride dropwise to the reaction kettle. After 2 hours, the feeding of the barium chloride aqueous solution is completed. Lower the temperature of the reaction system in the reaction kettle to -5 - -10 °C, age for 8 hours, then centrifuge and wash with deionized water 2 - 3 times. Send the obtained powder product into a vacuum drying oven at 50 - 60 °C and dry for 12 hours to obtain 6.65 g of a white powder modified barium sulfate (Ⅰ-6) product. The SEM of this modified barium sulfate powder (Ⅰ-6) product shows that it is irregular particles with a particle size of 65 - 175 nm. The IR (KBr tablet, cm -1 ) spectrum of the modified barium sulfate powder product (Ⅰ-6) is basically the same as that of the white modified barium sulfate powder material (Ⅰ-2) in Example 6, indicating that the modified barium sulfate powder product (Ⅰ-6) contains structural units such as CH3, CH2, C=C, C=O, P=O, C-O, etc., and it is confirmed that this white powder product is a coprecipitation powder of zinc ammonium N-(2-methacryloyloxyethyl)-N-dodecyl-N,N-bis(ethyl-2-phosphonic acid) chloride dihydrate of formula-(3) and barium sulfate.

[0047] Modified barium sulfate powder (Ⅰ-7) of Example 11

[0048] According to the method and operation steps of Example 5, change “... After cooling, use an aqueous sodium hydroxide solution with a mass percentage concentration of 30% to adjust the pH of the reaction product system in the reaction kettle to 7.5, let it stand and remove the water-insoluble substances in the aqueous phase. Slowly add 158 grams of an aqueous silver nitrate solution with a mass percentage concentration of 25% to the obtained organic phase...” to “... After cooling, use an aqueous sodium hydroxide solution with a mass percentage concentration of 30% to adjust the pH of the reaction product system in the reaction kettle to 7.5, let it stand and remove the water-insoluble substances in the aqueous phase. Slowly add it to 450 grams of an aqueous solution containing 6.8 grams of sodium sulfate and 0.018 grams of 4-oxo-2,2,6,6-tetramethylpiperidine...” Subsequently, slowly add 550 grams of an aqueous solution containing 6.8 grams of barium chloride dropwise to the reaction kettle. After 2 hours, the feeding of the barium chloride aqueous solution is completed. Lower the temperature of the reaction system in the reaction kettle to -5 to -10 °C, age for 8 hours, then centrifuge and wash with deionized water 2 to 3 times. Send the obtained powder product to a vacuum drying oven at 50 to 60 °C and dry for 12 hours to obtain 8.93 grams of a white powder-like modified barium sulfate (Ⅰ-7) product. The SEM of the modified barium sulfate powder (Ⅰ-7) shows that it is irregular particles with a particle size of 50 to 245 nm. The IR (KBr tablet, cm -1 ) spectrum of the modified barium sulfate powder material (Ⅰ-7) is basically the same as that of the white modified barium sulfate powder material (Ⅰ-1) in Example 5, indicating that the modified barium sulfate powder (Ⅰ-7) contains structural units such as methyl, CH2, benzene ring, C═C, C═O, P═O, C-O, etc., and confirming that the white powder product is a coprecipitation powder of barium N-(2-methacryloyloxyethyl)-N-benzyl-N,N-bis(ethyl-2-phosphonate) ammonium chloride and barium sulfate. <> <>

[0049] Antibacterial properties of the modified barium sulfate powder in Example 12 <> <>

[0050] Refer to the methods and operation steps specified in GBT 21510-2008 "Testing Methods for Antibacterial Properties of Nano-inorganic Antibacterial Materials". Weigh 1.0000 gram of the unsaturated quaternary ammonium bisphosphonate modified barium sulfate powder in Examples 5 to 11 respectively, and mix it with 5.0 mL of a suspension of Staphylococcus aureus (S. aureus) or Escherichia coli (E. coli) with a concentration of 1×10<> 6 [[ID=,10]]CFU / mL, and add them together to 95 mL of a phosphate buffer solution containing 0.1% Tween-80. After oscillating and culturing in a constant temperature incubator at 37 °C for 2, 12, or 24 hours, count the total number of remaining viable bacteria colonies to quantitatively evaluate the antibacterial performance of the modified barium sulfate powder. The results are shown in Table 1. <> <>

[0051] Table 1 Antibacterial properties of the modified barium sulfate powder <> <>

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[0053] From the preliminary antibacterial performance test results of the unsaturated quaternary ammonium bisphosphonate modified barium sulfate powder in Examples 5 to 11, the antibacterial activity order of metal cations is Ag + >Zn 2+ >Ba 2+ >Ca 2+ , the activity of dodecyl in quaternary ammonium cations to kill pathogenic bacteria is higher than that of benzyl, and the smaller the particle size of the unsaturated quaternary ammonium bisphosphonate modified barium sulfate powder material, the higher the antibacterial activity. The unsaturated quaternary ammonium bisphosphonate soluble in water at 50-60 °C is not only an organic double salt co-precipitated with barium sulfate, but also a surfactant for preparing nano barium sulfate.

Claims

1. Application of an unsaturated quaternary ammonium bisphosphonate in preparing modified barium sulfate powder, which is achieved through the following steps: sequentially weigh deionized water, unsaturated quaternary ammonium bisphosphonate, sulfate, and inhibitor and feed them into a reaction kettle; after purging oxygen with nitrogen in the reaction kettle, control the temperature at 20 - 100 °C, stir evenly, then slowly add an aqueous barium salt solution to the reaction kettle. After the feeding of the aqueous barium salt solution is completed, lower the temperature of the reaction system in the reaction kettle to -10 - 25 °C, age for 2 - 12 hours, and then separate, wash, and dry to obtain an unsaturated quaternary ammonium bisphosphonate modified barium sulfate powder material; characterized in that The unsaturated quaternary ammonium bisphosphonate has the structure shown in general formula (Ⅰ): Among them, R in the general formula (I) is selected from H or CH3, and R1 is selected from C1-C 18 hydrocarbon group, and M n+ is selected from Na + , K + , Ag + , Ca 2+ , Co 2+ , Cu 2+ , Fe 2+ , Mg 2+ , Mn 2+ , Zn 2+ , Sr 2+ , Al 3+ , Bi 3+ , Cr 3+ , Fe 3+ , Sn 4+ , Ti 4+ , Zr 4+ , one of N-benzyl-N,N,N-trimethylammonium cation, N-benzyl-N,N,N-triethylammonium cation, N-benzyl-N,N,N-tributylammonium cation, N,N,N,N-tetrabutylammonium cation, N-dodecyl-N,N-dimethyl-N-benzylammonium cation, N-dodecyl-N,N-diethyl-N-benzylammonium cation, N-tetradecyl-N,N-dimethyl-N-benzylammonium cation or N-tetradecyl-N,N-diethyl-N-benzylammonium cation, where n is selected from one of 1, 2, 3 or 4, and X - is selected from Cl - , Br - or NO3 - ; The dosage ratio of the unsaturated quaternary ammonium bisphosphonate / sulfate / barium salt / inhibitor / deionized water is 5 - 50:10 - 150:10 - 150:0.15 - 1.5:50 - 5000.

2. The use of an unsaturated quaternary ammonium bisphosphonate according to claim 1 in the preparation of modified barium sulfate powder, characterized in that The sulfate refers to one or more of sodium sulfate, potassium sulfate, ammonium sulfate, magnesium sulfate, aluminum sulfate, and zinc sulfate.

3. Use of an unsaturated quaternary ammonium bisphosphonate as claimed in claim 1 in the preparation of a modified barium sulfate powder, characterized in that The aqueous barium salt solution refers to dissolving the barium salt in deionized water, filtering out insoluble impurities, and then preparing an aqueous barium salt solution with a mass percentage concentration of 0.2 - 250‰; Wherein the barium salt refers to one of barium chloride, barium bromide, and barium nitrate.

4. Use of an unsaturated quaternary ammonium bisphosphonate as claimed in claim 1 in the preparation of a modified barium sulfate powder, characterized in that The inhibitor refers to vitamin C or 4 - oxo - 2,2,6,6 - tetramethylpiperidine.

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